Hydroxytyrosol for Colorectal Cancer

Overseen By Kimberly Vu Clinical Research Nurse, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The Methodist Hospital Research Institute

Must be taking: 5FU-based therapy

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Cardiac abnormalities, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Up to 100 weeks

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase I study investigating the safety and antitumor activity of 5FU-based therapy (FOLFIRI/FOLFOX + Biologics) in combination with Hydroxytyrosol (HT) as a treatment for patients with advanced or metastatic colorectal cancer. Patients will receive: 1 capsule of HT 25 mg daily for 2 weeks before beginning 5FU-based therapy (FOLFIRI/FOLFOX + Biologics), 1 capsule of HT (25 mg) daily for 2 weeks while receiving the FOLFIRI/FOLFOX + Biologics, until sign of disease progression. The prescribed FOLFIRI/FOLFOX administer as: Irinotecan 180 mg/m² intravenously (IV) over 90 minutes concurrently with Leucovorin 400 mg/m² IV over 120 minutes, followed by Fluorouracil 400-500 mg/m² IV bolus then 2400-3000 mg/m² IV infusion over 4-6 hours with or without, the designated Biologics, a standard dose of Cetuximab or Bevacizumab will be administered in 2-week cycles until disease progression or un-tolerated toxicity

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients receiving certain treatments like corticosteroids or investigational agents may not be eligible, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Hydroxytyrosol for colorectal cancer?

Research shows that Hydroxytyrosol, a compound found in olive oil, can slow down the growth of cancer cells and trigger their self-destruction in colorectal cancer cell studies. It has also shown similar effects in other types of cancer, suggesting it might help fight cancer by stopping cell growth and promoting cell death. ^{1 2 3 4 5}

Is hydroxytyrosol safe for human use?

Hydroxytyrosol, a compound found in olive oil, has been evaluated for safety, and a study suggests a No Observed Adverse Effects Level (NOAEL) of 500mg/kg/day, indicating it is generally safe at this dosage. ^{2 3 4 6 7}

How is the drug Hydroxytyrosol unique in treating colorectal cancer?

Hydroxytyrosol, a compound found in olive oil, is unique because it acts as a powerful antioxidant and can induce cancer cell death (apoptosis) and inhibit cell growth in colorectal cancer. Unlike traditional treatments, it targets specific genes involved in cell death and has shown potential in various cancer types, making it a novel option for colorectal cancer therapy. ^{1 2 3 4 8}

Research Team

Abdullah Esmail, MD

Principal Investigator

Houston Methodist Neal Cancer Center

Eligibility Criteria

This trial is for patients with advanced or metastatic colorectal cancer. Participants must be suitable for 5FU-based therapy and able to take daily capsules of Hydroxytyrosol (HT). Specific inclusion and exclusion criteria are not provided, but typically involve factors like overall health, prior treatments, and the stage of cancer.

Inclusion Criteria

I am fully active or can carry out light work.

My colorectal cancer is confirmed to be advanced or has spread.

Life expectancy ≥6 months

Exclusion Criteria

I have hepatitis B, C, or HIV that is not under control.

Serum albumin <2.8 g/dL

Total bilirubin >1.5 × ULN or >1.5 mg/dL

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants receive 1 capsule of HT 25 mg daily for 2 weeks before beginning 5FU-based therapy

2 weeks

1 visit (in-person)

Treatment

Participants receive 5FU-based therapy (FOLFIRI/FOLFOX + Biologics) in combination with HT until disease progression or un-tolerated toxicity

Up to 100 weeks

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Hydroxytyrosol

Trial Overview The study tests the safety and effectiveness of adding HT to standard chemotherapy regimens (FOLFIRI/FOLFOX + Biologics) in treating colorectal cancer. Patients will take HT daily before and during their chemo cycles until disease progression or unacceptable side effects occur.

Participant Groups

Group I: Hydroxytyrosol (HT) in combination with Folfiri/Folfox Experimental Treatment 1 Intervention

Patients will receive: 1 capsule of HT 25 mg daily for 2 weeks before beginning 5FU-based therapy (FOLFIRI/FOLFOX + Biologics), 1 capsule of HT (25 mg) daily for 2 weeks while receiving the FOLFIRI/FOLFOX + Biologics, until sign of disease progression. The prescribed FOLFIRI/FOLFOX administer as: Irinotecan 180 mg/m² intravenously (IV) over 90 minutes concurrently with Leucovorin 400 mg/m² IV over 120 minutes, followed by Fluorouracil 400-500 mg/m² IV bolus then 2400-3000 mg/m² IV infusion over 4-6 hours with or without, the designated Biologics, a standard dose of Cetuximab or Bevacizumab will be administered in 2-week cycles until disease progression or un-tolerated toxicity

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Findings from Research

Hydroxytyrosol, a compound found in olive oil, significantly reduces the viability of thyroid cancer cells (papillary and follicular) at high doses by promoting apoptosis and altering key cell cycle regulators like cyclin D1 and p21.

This study is the first to demonstrate that hydroxytyrosol induces cell death in thyroid cancer cells through the intrinsic apoptotic pathway, suggesting its potential as a novel therapeutic target for thyroid cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells. Toteda, G., Lupinacci, S., Vizza, D., et al.[2018]

Hydroxytyrosol significantly increases the expression of the CASP3 gene and the BAX:BCL2 ratio in human colorectal cancer cells, suggesting it may promote apoptosis (cell death) in these cancer cells.

The treatment with hydroxytyrosol also enhances the activity of key antioxidant enzymes and reduces oxidative stress, indicating its potential role in both reducing cancer cell proliferation and improving the antioxidant defense system in colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Hydroxytyrosol on Expression of Apoptotic Genes and Activity of Antioxidant Enzymes in LS180 Cells. Hormozi, M., Salehi Marzijerani, A., Baharvand, P.[2022]

Nano-capsulated hydroxytyrosol demonstrated significantly greater cytotoxic effects on HT-29 colorectal cancer cells compared to free hydroxytyrosol, with an IC50 of 6 PPM versus 12 PPM after 72 hours, indicating enhanced efficacy of the nano-formulation.

The study found that nano-capsulated hydroxytyrosol effectively induced cell cycle arrest by upregulating the CDKN1A and CDKN1B genes while downregulating the CCND1 gene, suggesting a specific mechanism of action in combating colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of the Anti-Cancer Effects of Free and PLGA-PAA Encapsulated Hydroxytyrosol on the HT-29 Colorectal Cancer Cell Line. Sani, NS., Onsori, H., Akrami, S., et al.[2022]

In a study involving 28 female Sprague-Dawley rats with induced mammary tumors, hydroxytyrosol significantly inhibited tumor growth and proliferation, showing results comparable to the chemotherapy drug doxorubicin, but with better histopathological outcomes.

Hydroxytyrosol altered the expression of genes related to important cellular processes such as apoptosis and cell cycle regulation, particularly enhancing the expression of Sfrp4, indicating its potential as an anti-cancer agent through multiple biological pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours. Granados-Principal, S., Quiles, JL., Ramirez-Tortosa, C., et al.[2015]

Hydroxytyrosol, a key antioxidant in virgin olive oil, significantly inhibits the proliferation of cancer cells, specifically human promyelocytic leukaemia (HL60) and colon adenocarcinoma (HT29) cells, at concentrations of approximately 50 and 750 micromol/l, respectively.

The compound induces apoptosis in HL60 cells at concentrations between 50 to 100 micromol/l and causes cell cycle arrest in the G0/G1 phase, suggesting that hydroxytyrosol may play a protective role against cancer by targeting tumor cells while showing no harmful effects on normal human lymphocytes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. Fabiani, R., De Bartolomeo, A., Rosignoli, P., et al.[2019]

Hydroxytyrosol, a phenolic compound from olives, is being explored for its potential use as a supplement and preservative in various industries, including nutraceuticals and cosmetics.

The toxicological evaluation of hydroxytyrosol suggests a No Observed Adverse Effects Level (NOAEL) of 500 mg/kg/day, indicating a favorable safety profile for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicological evaluation of pure hydroxytyrosol. Auñon-Calles, D., Canut, L., Visioli, F.[2013]

Hydroxytyrosol (HT) demonstrated significant anticancer effects in human leukemia T cells (Jurkat and HL60), with an IC50 of 27.3 µg/mL for Jurkat cells, indicating its potential as a natural treatment for liquid cancers.

HT also exhibited anti-inflammatory properties by reducing nitric oxide levels in murine macrophages (Raw264.7), suggesting it could be beneficial in managing inflammation alongside its anticancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involvement of the PI3K/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity. Parra-Perez, AM., Pérez-Jiménez, A., Gris-Cárdenas, I., et al.[2022]

Hydroxytyrosol (HT) effectively inhibits the growth of prostate cancer cells (LNCaP and C4-2) in a dose-dependent manner while showing no harmful effects on normal prostate cells, indicating its cancer-specific action.

HT induces cell cycle arrest and apoptosis in prostate cancer cells by affecting key signaling pathways, including inhibition of cyclins and activation of apoptotic markers, suggesting its potential as a safe and effective treatment for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells. Zubair, H., Bhardwaj, A., Ahmad, A., et al.[2018]

References

1. Italy pubmed.ncbi.nlm.nih.gov

High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Effects of Hydroxytyrosol on Expression of Apoptotic Genes and Activity of Antioxidant Enzymes in LS180 Cells. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A Comparison of the Anti-Cancer Effects of Free and PLGA-PAA Encapsulated Hydroxytyrosol on the HT-29 Colorectal Cancer Cell Line. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Toxicological evaluation of pure hydroxytyrosol. [2013]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Involvement of the PI3K/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells. [2018]